Tritrichomonas foetus is a flagellated parasite that primarily infects the reproductive tissues of livestock, causing bovine trichomoniasis. The cytoplasmic membrane of T. foetus contains various ...compounds that contribute to adherence, colonization, and pathogenicity. Metronidazole (MTZ) is the main treatment for trichomoniasis, but the emergence of drug‐resistant strains is a concern due to improper use and dosing. T. foetus infection induces inflammation, and macrophages are key players in the immune response. However, our understanding of the host's immune response to T. foetus is limited, and the specific mechanisms underlying these responses are not well understood. This study aimed to investigate the impact of T. foetus surface proteins from trophozoites cultured under different sublethal MTZ conditions (MTZ‐treated T. foetus MPs) on macrophage activation. By analyzing cytokine levels and gene expression in murine macrophages, we demonstrated that MTZ‐treated T. foetus MPs induce a specific proinflammatory response. MTZ‐treated T. foetus MPs‐exposed macrophages exhibited a higher NO and H2O2 production and overexpression of iNOS and NOX‐2 genes in comparison to untreated T. foetus. Additionally, MTZ‐treated T. foetus MPs triggered a significant induction of the proinflammatory cytokines IL‐1β, IL‐6, TNF‐α, and IFN‐γ, as well as the overexpression of the TLR4, MyD88, and NF‐κB genes on murine macrophages. The study aimed to unravel the immunological response and potential proinflammatory pathways involved in T. foetus infection and MTZ stress. Understanding the immune responses and mechanisms through which T. foetus surface proteins activate macrophages can contribute to the development of new therapeutic strategies for controlling bovine trichomoniasis.
Tritrichomonas foetus is a protozoan parasite that causes a venereal disease in cattle limiting reproduction by abortions and sterility. The immune response against this parasite is poorly ...understood. Since the iron and calcium ions are important regulators of the microenvironment of the urogenital tract in cattle, we decided to evaluate the role of these divalent cations on the antigenicity of membrane proteins of T. foetus on macrophage activation as one of the first inflammatory responses towards this pathogen. Colorimetric methods and ELISA were used to detect the nitric oxide and oxygen peroxide production and expression of cytokines in culture supernatant from macrophage incubated with membrane proteins from T. foetus cultured in iron‐ and calcium‐rich conditions. qRT‐PCR assays were used to evaluate the transcript expression of genes involved in the inflammatory response on the macrophages. The membrane proteins used for in vitro stimulation caused the up‐regulation of the iNOS and NOX‐2 genes as well as the generation of NO and H2O2 in murine macrophages on a dependent way of the metal concentrations. Additionally, after stimulation, macrophages showed a considerable rise in pro‐inflammatory cytokines and a downregulation of anti‐inflammatory cytokines, as well as up‐regulation in the transcription of the TLR4 and MyD88 genes. These data suggest that membrane proteins of T. foetus induced by iron and calcium can activate an inflammatory specific macrophage response via TLR4/MyD88 signalling pathway.
During angiogenesis, new vessels emerge from existing endothelial lined vessels to promote the degradation of the vascular basement membrane and remodel the extracellular matrix (ECM), followed by ...endothelial cell migration, and proliferation and the new generation of matrix components. Matrix metalloproteinases (MMPs) participate in the disruption, tumor neovascularization, and subsequent metastasis while tissue inhibitors of metalloproteinases (TIMPs) downregulate the activity of these MMPs. Then, the angiogenic response can be directly or indirectly mediated by MMPs through the modulation of the balance between pro- and anti-angiogenic factors. This review analyzes recent knowledge on MMPs and their participation in angiogenesis.
Pentacyclic triterpenes are found in a great variety of natural products and constitute an organic template for the development of new derivative compounds with therapeutic applications. In the ...present work, lupeol acetate isolated from Chrysophyllum cainito L. fruit was used as a template for the synthesis of novel N-alkyl-arylsulfonamide derivatives, and their synergistic effects with metronidazole against strains of Trichomonas vaginalis were tested. A library of 18 derivatives was synthesized. Ten compounds exhibited an IC
50
< 100 μM against a metronidazole-sensitive strain of T. vaginalis. Only seven of these compounds (12, 15, 18-22) also showed activity against metronidazole-resistant strains. The compounds 20 (N-cyclohexyl-p-chlorobenzenesulfonamidolupeol acetate) and 22 (N-cyclohexyl-p-nitrobenzenesulfonamidolupeol acetate) exhibited a similar IC
50
against both susceptible and resistant T. vaginalis strains and enhanced the efficacy of metronidazole in a partial and total synergistic way, respectively. These data provided evidence of the trichomonicidal effect of N-alkyl-arylsulfonamide derivatives of lupeol acetate, representing highly promising novel antiparasitic agents.
Copper is a trace element of biological significance that can form complexes with several thiol containing compounds which can be used as filler in biomedical polyurethanes. In this work, segmented ...polyurethanes (SPUs) were synthesized with thiol containing compounds as chain extenders including d-penicillamine (DP), l-penicillamine (LP), l-cysteine (LC) and reduced glutathione (GR). Then, the synthesized polyurethane was filled with copper chelates based on the same chain extenders. Evidence of free thiol containing chain extender in polyurethane was not observed by FTIR and Raman but EDX provided evidence of sulfur in the unfilled polyurethane and copper and sulfur in their composite. DSC and DRX showed the semi-crystalline nature of the polyurethanes which provided good mechanical properties, especially to those prepared with DP. The T
g
of the PCL determined by DMA shifted toward higher temperatures by the addition of copper complexes while TGA studies showed that the thermal degradation was slightly improved when LCCu and GRCu complex were added. Macrophage viability was observed in all composition studied after longer times of extraction (72 h) and dilutions (1:2 to 1:32) but remarkably high in those prepared with LCCu and GRCu. The anti-inflammatory response was proved in LC and GR copper complex filled polyurethanes as IL-4 and IL-10 increased with time while IL-1β and TNF-α were reduced.
Trichomonas vaginalis is the etiological agent of human trichomoniasis. Metronidazole has high treatment success rate among trichomoniasis patients. However, metronidazole‐resistant T. vaginalis has ...been reported, contributing in an increasing number of refractory cases. The mechanism of metronidazole resistance in this parasite is still unclear. In the vaginal environment, where the microaerophilic conditions prevail but the iron concentration is constantly fluctuating, the metronidazole resistance profile of T. vaginalis could be altered. In this study, we developed metronidazole‐resistant strains of T. vaginalis and evaluate if iron availability is important to the action of the drug. The modulation of iron levels and iron chelation affected the actions of metronidazole both in susceptible and resistant strains. Interestingly, the early resistant strains exhibited minor iron content. The results of transcription analysis in the early resistant strains showed dysregulation in the expression of genes that codified proteins involved in iron transporter, iron–sulfur cluster assemblage, and oxidative stress response, which could not be observed in the late resistant and susceptible strains. Our results indicate that iron content plays an important role in the metronidazole action in T. vaginalis and likely to be related to iron–sulfur proteins involved in metronidazole activation and oxidative stress via Fenton reaction.
Knowledge about the influence of early developmental factors on cardiometabolic health in the Maya is limited.
To analyse the relationship between birthweight (BW) and cardiometabolic parameters in a ...sample of rural Maya children from Yucatan, Mexico.
We took anthropometric measurements and obtained data on BW and fasting blood samples in a sample of 75 children aged 5-14 years. Dependent variables were: fat mass index (FMI), body mass index (BMI), glucose (G), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), LDL/HDL and TC/HDL ratios and metabolic index (TGxG/HDL
). Outcomes were transformed to
= 100 log(e)x and the resulting estimates are interpreted as symmetrical percentage differences. The main independent variable was BW z-score. Multiple linear regression analyses were used to assess the relationship between BW and outcomes.
An increase of one standard deviation in BW predicted 6.6% (95% CI -11.6, -1.6) decrease in HDL and 11% (95% CI 3.7, 18.4), 7.8% (95% CI 2.3, 13.2) and 19.6% (95% CI 3.1, 36) increases in LDL/HDL, TC/HDL and metabolic index, respectively.
Higher birthweights were associated with adverse levels of biochemical parameters in this sample of rural Maya children.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Inflammation is considered to be a major risk factor for the pathogenesis of chronic non-communicable diseases. Macrophages are important immune cells, which regulate inflammation and host defense by ...secretion of proinflammatory mediators. Obtaining biopeptides by enzymatic hydrolysis adds value to proteins of vegetative origin, such as
Mucuna pruriens
L. The present study evaluated the effect of enzymatic digestion of protein derivatives obtained from
M
.
pruriens
L. on the production of proinflammatory mediators by BALB/c mouse macrophages. Five different molecular weight peptide fractions were obtained (F > 10, 5–10, 3–5, 1–3, and < 1 kDa, respectively). At 300 μg/mL, F5–10 kDa inhibited 50.26 and 61.00% NO and H
2
O
2
production, respectively. Moreover, F5–10 kDa reduced the IL-6 and TNFα levels to 60.25 and 69.54%, respectively. After enzymatic digestive simulation, F5–10 kDa decreased the inflammatory mediators.
Trichomoniasis, caused by the protozoan parasite Trichomonas vaginalis, is the most common nonviral sexually transmitted infection worldwide. Although drug treatment is available, unpleasant side ...effects and increased resistance to the nitroimidazole family have been documented. Hence, there is a need for the identification of new and safe therapeutic agents against T. vaginalis. Antimicrobial activity of anthraquinone compounds has been reported by a number of authors. The genus Morinda is well known for the diversity of anthraquinones with numerous biological activities. A new anthraquinone, lucidin‐ω‐isopropyl ether, was isolated from the roots of Morinda panamensis Seem. The structure of the compound was determined by 1H and 13C Nuclear Magnetic Resonance (NMR) analyses, in addition to comparison with literature reports. Using in vitro susceptibility assay, the half inhibitory concentration (IC50) of lucidin‐ω‐isopropyl ether for T. vaginalis (1.32 μg/mL) was found similar to that of metronidazole concentration tested (6 μM = 1.03 μg/mL). In addition, this anthraquinone was capable of inhibiting the parasite's ability to kill HeLa cells and decreased proteolytic activity of the proteinase TvMP50 from T. vaginalis. This was associated with the decreased expression of the mp50 gene. These results demonstrate the trichomonicidal potential by lucidin‐ω‐isopropyl ether. Further action‐mode studies are necessary to elucidate the antiparasitic mechanism of this new anthraquinone to develop a more potent antitrichomonal agent.
Salvia tiliifolia Vahl (Lamiaceae) is used for the empirical treatment of pain and inflammation. The diterpenoid tilifodiolide (TFD) was isolated from Salvia tiliifolia. The in vitro ...anti‐inflammatory effects of TFD (0.1–200 µM) were assessed using murine macrophages stimulated with LPS and estimating the levels of pro‐inflammatory mediators for 48 h. The in vivo anti‐inflammatory activity of TFD was assessed using the carrageenan‐induced paw edema test for 6 h. The antinociceptive effects of TFD were evaluated using the formalin test and the acetic acid induced‐writhing test. The effects of TFD on locomotor activity were assessed using the open field test and the rotarod test. TFD inhibited the production of TNF‐α (IC50 = 5.66 µM) and IL‐6 (IC50 = 1.21 µM) in macrophages. TFD (200 mg/kg) showed anti‐inflammatory effects with similar activity compared to 10 mg/kg indomethacin. The administration of TFD induced antinociception in the phase 1 (ED50 = 48.2 mg/kg) and the phase 2 (ED50 = 28.9 mg/kg) of the formalin test. In the acetic acid assay, TFD showed antinociceptive effects (ED50 = 32.3 mg/kg) with similar potency compared to naproxen (ED50 = 36.2 mg/kg). In the presence of different inhibitors in the acetic acid assay, only the co‐administration of TFD and naloxone reverted the antinociceptive activity shown by TFD alone. TFD did not affect locomotor activity in mice. TFD exerts in vitro and in vivo anti‐inflammatory activity and in vivo antinociceptive effects.
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